title: Clonal composition of neuroantigen-specific CD8+ and CD4+ T-cells in multiple sclerosis.
abstract: Patients with multiple sclerosis (MS) show a high prevalence of myelin-reactive CD8+ and CD4+ T-cell responses, which are the putative effectors/modulators of CNS neuropathology. Utilizing a novel combination of short-term culture, CFSE-based sorting and anchored PCR, we evaluated clonal compositions of neuroantigen-targeting T-cells from RRMS patients and controls. CDR3 region analysis of TCRβ chains revealed biased use of specific TCRBV-bearing CD4+ clones. CD8+ clones showed homology to published TCR from CNS-infiltrating T-cells in MS lesions. These studies are the first description of TCR usage of CNS-specific CD8+ T-cells and provide insights into their potential regulatory role in disease.
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Biegler
authors.forename: Shirley X
authors.initials: SX
authors.lastname: Yan
authors.forename: Sterling B
authors.initials: SB
authors.lastname: Ortega
authors.forename: Deepani K
authors.initials: DK
authors.lastname: Tennakoon
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.forename: Nitin J
authors.initials: NJ
authors.lastname: Karandikar
mesh_terms: D000328:Adult; D000906:Antibodies / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D003001:Cloning, Molecular; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000473:pathology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000276:immunology; D011948:Receptors, Antigen, T-Cell
chemical_list: D000906:Antibodies; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D011948:Receptors, Antigen, T-Cell